Transcriptional regulation by epigenetic processes has been implicated in the aetiology of many diseases. In cancer, aberrant epigenetic silencing of genes implicated in tumorigenesis and progression has been observed in all tumour types. Epigenetic silencing can be associated with repressive histone marks, such as H3K27me3 (3). The epigenetic H3K27me3 repressive mark is executed and maintained by the polycomb repressive (PRC2) complex via its HKMT catalytic subunit EZH2 (5). EZH2 along with EED and SUZ12 are the indispensible core components of PRC2. Unlike most other epigenetic marks that are mediated by multiple enzymes, the trimethylation of H3K27 appears to be mediated primarily by EZH2 suggesting EZH2 inhibition as a key target for development of epigenetic therapies (6). EZH2 over-expression is a prognostic marker for shorter patient survival for a variety of cancers (9-11). It has been implicated in tumor angiogenesis (12), while mouse models demonstrated its role in driving tumorgenesis (13). Furthermore, maintenance of cancer stem cells seems to depend on EZH2 expression and knock-down of EZH2 in tumour cells blocks tumour cell growth (14-16). Thus, there is strong evidence that inhibition of EZH2 may be useful for the treatment of cancer, and it would be desirable to identify small molecule inhibitors of that target.
Small molecule inhibitors of EZH2 based on indole (A) and azaindazole cores (B) have previously been described, see WO2011/140324 and WO2012/005805.

However, there remains a need for further compounds having useful EZH2 inhibitory effects.
The aminoquinazoline compound BIX-01294 (see structure (C) below) and related compounds have been described as having activity against the protein lysine methyltransferase G9a (see J. Med. Chem. 2011, 54 (17), p. 6139-6150)
